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The sugar disease--understanding type 2 diabetes mellitus.

In 2001 there were 125,000 people with diabetes in New Zealand. Numbers were predicted to increase to 180,000 by 2011. (1) This number has been outstripped: 270,000 people have diagnosed diabetes with probably another 100,000 undiagnosed. (2,3) Of these, about 90 percent have type 2 diabetes (T2DM). (4) By 2021, T2DM and its complications will be consuming 15 percent of the total health budget. (5)

Disparities exist in prevention, diagnosis, treatment and outcomes of T2DM within New Zealand communities. Nurses are at the vanguard of diabetes care and roles for diabetes nurse specialists are being expanded. The increasing prevalence of T2DM in the population guarantees that all nurses will, at some time, be caring for people with this condition. Nurses must also play a role in rein farting the public health messages around T2DM risk factors and prevention and screening programmes.

An understanding of the causes, pathophysiology and treatment of T2DM enhances the provision of quality care.


After reading this article and completing the accompanying online learning activities, you should be able to:

* Outline the normal controls of plasma glucose.

* Describe current understanding of the causes of T2DM.

* Explain the signs and symptoms of T2DM in relation to its pathophysiology.

* Discuss complications of diabetes.

* Review current and emerging management strategies for T2DM including drug therapies.


Worldwide, there is an epidemic of type 2 diabetes mellitus (T2DM), Largely associated with increased rates of obesity and decreased physical activity. (6) Deaths occurring from T2DM are predicted to double in the next two decades, with 80 percent of deaths occurring in middle and Low-income nations. (6)

New Zealand is aLso experiencing a rapid rise in the number of people diagnosed with T2DM. At the same time, specialist resources are being cut back or underfunded. (7) There are disparities in incidence and outcomes of T2DM within different groups in New Zealand, the prevalence in Maori, Pacific and Asian populations being three times that of the general population. (2) Maori with T2DM are eight times more Likely to develop renal failure and four times more Likely to require lower Limb amputation than non-Maori diabetics. (8)

Care for individuals with T2DM should be supported by good understanding of the underlying pathophysiology of the disease. Nurses providing care for other health issues to patients with T2DM must be able to integrate that care with ongoing management of plasma glucose levels.

Diabetes is a metabolic disorder characterised by high plasma glucose concentrations (PGC) and abnormal insulin activity in the body. Type 1 diabetes (T1DM) is distinguished by an absolute Lack of insulin, due to autoimmune failure of beta cells in the pancreas through largely unknown causes. (9) The pathophysiology of T2DM is more complex. For both forms of diabetes, uncontrolled hyperglycaemia leads to a variety of complications, including retinopathy, peripheral neuropathy and nephropathy, and a high risk of cardiovascular disease.


Plasma glucose concentration (PGC) is normally maintained between 4-6 millimoles per litre (mmol/L). In T2DM, PGC is consistently elevated above 11mmol/L (random) or above 7mmol/L when fasting. (10) Classically, T2DM has been explained as impaired insulin secretion, combined with decreased sensitivity of peripheral tissues to its actions. It is now recognised that, just as regulation of glucose involves a complex interaction of many hormones and feedback mechanisms, the disordered glucose metabolism evident in T2DM is also multifactorial. Key players are insulin, glucagon, amylin, and the incretins (table 1, p17).


Insulin is synthesised in the beta cells of the pancreas and stored until released by exocytosis. Secretion occurs mainly in response to raised PGC. Other triggers are shown in table 1. (11) Normally, following a meat there is a biphasic response: a sharp rise in insulin secretion, lasting 10 to 15 minutes, followed by a slower, delayed increase. This biphasic response is absent in T2DM (figure 1, p18).

After secretion, insulin binds to cell receptors in peripheral tissues (particularly the liver, skeletal muscle and adipose tissue). This triggers the insertion of glucose transporter molecules into the target cell membrane, allowing glucose into the cell. Glucose is then used to manufacture adenosine triphosphate (ATP) or stored as glycogen or lipids (figure 2). Insulin aLso increases the transport of potassium (K+), amino acids and calcium into cells. (11) Insulin directs glucose use within the cell. When insulin binds to its receptor, more glucose is used to manufacture glycogen in skeletal muscle and liver cells, and lipogenesis occurs in adipose tissue. Protein synthesis is increased and breakdown of fats (lipolysis) and glycogen (glycogenolysis) decreased.


Glucagon is synthesised in the alpha cells of the pancreas, in response to low PGC. Glucagon secretion is suppressed by high PGC but this response is absent in T2DM (figure 1), where plasma glucagon levels remain elevated after a meat. (12) This has a direct impact on the regulation of glucose in T2DM.

Glucagon increases PGC through a variety of mechanisms. It acts mainly on the liver, where it increases glycogen breakdown and gluconeogenesis, releasing glucose into the blood. This is important in the fasting state, as the brain relies on an adequate and continuous supply of glucose for normal function. Glycogenesis is inhibited. Amylin This hormone is stored and secreted with insulin in the beta cells of the pancreas. It acts via a series of pathways to inhibit glucagon secretion, decrease gastric emptying and promote satiety, thus reducing food intake. (13) Amylin can deposit and form plaques in the pancreas that may cause destruction of beta cells in the development of T2DM. (13,14)


These are hormones released by intestinal cells. The most important incretin in glucose regulation is the glucagon-like peptide (GLP-1). This hormone reduces pancreatic beta cell workload through a variety of mechanisms: (15)

[1.] Decreased rate of gastric emptying, which reduces the rate of nutrient absorption and thus insulin demand.

[2.] Increased sensation of satiety via central nervous mechanisms that reduce food intake.

[3.] Decreased glucagon secretion that reduces hepatic glucose production, thus reducing insulin demand.

[4.] GLP-1 may also increase beta cell proliferation and insulin synthesis.

After secretion, incretins are rapidly deactivated by the enzyme dipeptidyl peptidase-4 (DPP4). Once PGC is returned to normal, secretion of incretins is terminated. (15) GLP-1 concentrations are reduced in T2DM, which may account for continued high levels of glucagon secretion after meals.


Hyperglycaemia is the outcome of three key dysfunctions in T2DM: insulin resistance, insulin deficiency and abnormal glucagon synthesis. The causes of these three dysfunctions are not welt understood. There are upwards of 27 different genes thought to play a role in the development of T2DM. (12) People with a susceptible genetic make-up who also pursue a "diabetogenic" lifestyle (increased caloric intake, reduced physical activity) increase their risk of developing T2DM. It is worth remembering however, that T2DM is not exclusively associated with obesity and that people without the genetic predisposition, even if obese, do not develop T2DM.

Insulin resistance

Insulin resistance is normally present before the development of overt T2DM. It has been demonstrated in people with normal PGC, and in prediabetic states. (16) Insulin resistance naturally increases with age, in pregnancy, puberty and obesity, or in stress conditions where there are elevated levels of corticosteroid hormones. (17) Insulin resistance causes decreased glucose uptake and utilisation in skeletal muscle cells, abnormal uptake of lipids and fatty acids in adipose tissue and increased glucose production by the Ever.

Resistance to insulin may relate to abnormal receptor activity on target cell membranes (skeletal muscle, adipose or liver cells). Receptors may be damaged by oxidative stress or there may be down-regulation of receptor numbers in response to persistent elevated PGC.

Additionally, there may be damage to the pathways within target cells that allow utilisation of glucose (figure 2). Most insulin-mediated glucose storage occurs in skeletal muscle in the form of glycogen. Glycogenesis involves the activation of enzyme pathways by insulin. (17) Damage to pathways through oxidative stress or excess accumulation of free fatty acids may inhibit storage, increasing PGC.

Skeletal muscle cells may also have reduced or defective mitochondria. Mitochondria are the organelles inside cells responsible for the conversion of fuel sources (glucose and fatty acids) to ATP. If there is reduced mitochondrial function, fatty acids accumulate in the skeletal muscle cells and cause oxidative and inflammatory damage. Glucose uptake and utilisation are impaired. (16)

Accumulation of fatty acids in skeletal muscle and liver cells, along with associated inflammation and oxidative damage, is called lipotoxicity. Damage to cell molecules by glucose occurs through direct effects, and by the generation of free radicals (oxidative stress). This is termed glucotoxicity (figure 2, p19).


Beta cell dysfunction

In the initial stages of T2DM, there is increased secretion of insulin from beta cells in the pancreas. This hyperinsulinaemia is a response to abnormally elevated PGC, triggered by insulin resistance. However, even in the prediabetic stage, beta cell numbers and function are decreased. (16) More and more, the role of beta cell dysfunction is being thought of as the key factor in development of T2DM. (18)

The sequence of events for beta cell dysfunction appears to be: (19)

[1.] There is some form of genetic defect in pancreatic beta cells.

[2.] This defect impairs beta cell ability to respond to increasing demand caused by insulin resistance as it progresses. [3.] Beta cells are further damaged by the metabolic consequences of T2DM.

Early changes are evident in the toss of pulsatile secretion patterns and of the first phase response (figure 1). (20) There are a number of theories about causes of beta cell dysfunction. Glucotoxicity and/or lipotoxicity may cause oxidative (free radical) damage to beta cells genes and to synthesis and secretion pathways (figure 3).

Beta-cell exhaustion may also pray a rote in impaired responses. In this theory, the high rate of secretion by beta cells exhausts some factor required for insulin synthesis and production is reduced. (16) Lipotoxicity is also implicated in the increased rate of beta cell apoptosis (death).

Beta-cell loss, where apoptosis occurs without compensatory regeneration, has been demonstrated in T2DM. This is in contrast with obese, nondiabetic individuals where beta-cell mass is increased. (16) Beta cells seem particularly vulnerable to oxidative stress. Lipotoxicity and glucotoxicity may damage cells beyond repair, or other factors may be involved.

Amylin plaques have been found in beta cells and are believed, much like amyloid plaques in Alzheimer's disease, to cause cellular apoptosis. (13,14)

The rote of incretins in beta-cell regeneration is now being recognised. Lack of incretin (especially GLP-1) increases apoptosis and reduces beta-cell replication rates, at least in animal models. (21)

Abnormal glucagon secretion

Failure of suppression of glucagon secretion from the alpha cells of the pancreas contributes to hyperglycaemia in T2DM and is aLso seen in prediabetes. Glucagon stimulates liver production of glucose and also increases free fatty acid levels, contributing to lipotoxicity. Abnormal glucagon levels may occur due to loss of insulin which would normally suppress alpha cell activity. Incretins (GLP-1) also normally suppress glucagon secretion. In addition there may also be abnormal increase in alpha cell numbers as insulin levels decrease. (12)

The role of adipose tissue in T2DM

Obesity has been identified as the key risk factor for developing T2DM. (10) In 2007, 26.5 percent of New Zealand's adult population were obese (determined as a body mass index of more than 30kg per square metre). By ethnicity, 41.7 percent of Maori adults were obese, 63.7 percent of Pacific people, and 11 percent of Asian adults. At particular risk are those with predominantly abdominal fat deposits. (22)

Abdominal fat acts as an endocrine organ, releasing hormones and a variety of inflammatory mediators (adipokines) that affect lipid metabolism and directly impact on insulin resistance and beta cell function.

Increased concentrations of fatty acids and dyslipidaemia are associated with obesity. These contribute to insulin resistance and hyperglycaemia through lipotoxicity. (23)


There are intermediate states on the way to the development of outright T2DM. (23,24) Impaired fasting glucose (greater than 5.6mmol/L) and impaired glucose tolerance (between 7.8 and 11.1mmol/L at two hours post glucose challenge) are indicative of increasing insulin resistance and possibly declining beta cell function. (19) Impaired glucose control is included in the diagnosis of metabolic syndrome: a cluster of risk factors for cardiovascular disease and T2DM that are related to insulin resistance.

These factors are abdominal obesity, dyslipidaemia, impaired fasting glucose and hypertension. The use of metabolic syndrome as a diagnosis is subject to some debate (25) and has been omitted from the most recent cardiovascular guidelines. (26)


Classical symptoms of diabetes--polyuria, polydipsia and polyphagia--may not be as severe in T2DM as in type 1, often the person with T2DM is asymptomatic. Symptoms may be intermittent as PGC fluctuates. (14) Polyphagia, increased hunger due to cellular starvation, is uncommon in T2DM because there is usually some insulin present. Fatigue due to metabolic changes may be a feature.

Polyuria occurs when the amount of glucose being filtered by the kidneys overwhelms reabsorption mechanisms. In healthy kidneys, glucosuria occurs when PGC exceeds 10-12mmol/L. Glucose in the urinary filtrate generates an osmotic gradient preventing reabsorption of water. Hyperglycaemia causes production of Large volumes of dilute urine and loss of body water, causing postural hypotension and dehydration. (14)

Dehydration triggers compensatory responses, including release of anti-diuretic hormone (ADH) and triggering of the thirst mechanism. Due to the osmotic nature of the diuresis, ADH is ineffective in decreasing water loss through the kidneys. The thirst mechanism induces polydipsia.

More common manifestations of T2DM are due to the presence of excess glucose: this can predispose a person to recurrent infections, such as skin infections and vaginal thrush, accompanied by pruritis. (14) Blurred vision may occur due to osmotic changes in fluid levels in the eye, or with long-term damage causing retinopathy. Because symptoms are often insidious, a person with T2DM may present very late with diabetic complications already present.



Acute complications of diabetes are: hypoglycaemia, diabetic ketoacidosis (DKA), and hyperosmolar hyperglycaemic non-ketotic syndrome (HHNS, sometimes referred to as HONK). Hypoglycaemia occurs in relation to drug therapy. DKA is Less frequent in T2DM than HHNS. Key differences in pathophysiology between these two states are presented in table 2.

Essentially, both involve dehydration but DKA also includes a metabolic acidosis due to ketone production. In T2DM, there is normally sufficient insulin to inhibit ketogenesis. HHNS Lacks symptoms of ketoacidosis so there is often a more profound dehydration (10 or more litres of body water, compared with four to seven litres in DKA) and higher PGC when the person finally presents. (14,27)


Long-term complications of T2DM can be microvascular or macrovascular defects. Macrovascular complications include stroke, cardiovascular disease and peripheral vascular disease, and are the major cause of mortality for people with T2DM. Dyslipidaemia, lipotoxicity, glucotoxicity and activation of inflammatory mechanisms contribute to the development of atherosclerosis and subsequent macrovascular complications. Glycaemic control and cardiovascular risk are associated: each I percent drop in HbA1c decreases the 10-year risk of myocardial infarction by 14 percent. (10) Cardiovascular risk in T2DM is increased in the presence of nephropathy. (26) Intensive glycaemic and lipid control are essential for risk reduction.

Microvascular complications encompass neuropathies, nephropathy, retinopathy and encephalopathies. An increase of HbA1c (see box, p20) over seven percent increases the risk of microvascular complications significantly. However, any reduction of initial HbA1c is helpful: A two percent reduction results in risk reduction of around 60 percent for microvascular complications. (27)

Diabetic neuropathy

Impaired peripheral nerve function occurs in up to 50 percent of people with diabetes. (27) Frequently it is asymptomatic so regular screening is important. Glucotoxicity, lipotoxicity, oxidative stress and inflammation all contribute to nerve damage. Impaired oxygen and nutrient supply to neurons as a result of microvascular damage is also thought to be due to oxidative stress. (14,27)

Nervous tissue is also vulnerable via a separate mechanism. Glucose entry into nervous tissue is not regulated by insulin. In hyperglycaemic states, excess glucose enters neurons and is converted into sorbitol and then fructose via the polyol pathway. These sugars are unable to exit the cell as readily as glucose and become trapped, exerting an osmotic gradient causing intracellular oedema. This effect also occurs in the Lens of the eye, inducing cataract formation. (27)

Peripheral neuropathies occur either in the sensorimotor nerves or the autonomic nerves. Classical diabetic neuropathy is a bilateral sensory disturbance of hands and feet (table 3). Guidelines for assessment and treatment of the diabetic foot can be found at magazine/20l0/october/diabeticFoot.asp#key

Autonomic neuropathies are more immediately disruptive to body function and can be life-threatening. The 10-year mortality rate for symptomatic autonomic neuropathy is 25-50 percent. (27) Signs include orthostatic hypotension, incontinence (faecal and urinary), dysphagia, nausea and vomiting related to impaired gastric emptying and impotence.

Diabetic nephropathy

Damage to the kidneys with prolonged exposure to hyperglycaemia causes proteinuria, hypertension and renal failure. Risk is increased with dyslipidaemia and hypertension. (10) Maori are 8.8 times more likely to develop nephropathy as a consequence of diabetes than non-Maori.(8) Incidence is also increased in Pacific and Asian populations.

Underlying causes of nephropathy are similar to neuropathy, including the polyol pathway. The susceptibility of the kidneys to these factors is, in part, genetically determined. (28)

Initially there is Loss of regulation of blood flow through the glomerulus. This causes excess perfusion and filtration. Protein is lost in the urinary filtrate (microalbuminuria), and the glomerular basement membrane is damaged. ACE inhibitors protect against this damage, suggesting that Angiotensin II is somehow involved in causing nephropathy. (28,10) Progression to overt nephropathy from this stage is not inevitable and with aggressive therapy, renal damage can be contained or even reversed.


This microvascular complication is completely asymptomatic until damage is advanced and visual impairment permanent. Screening for diabetic retinopathy is essential to stabilise damage and preserve vision. Maori and Pacific people with diabetes are two to three times more Likely to have symptomatic retinopathy. (10)

Prolonged exposure to hyperglycaemia causes damage to blood vessels in the retina. White blood ceLLs are activated and attach to blood vessel walls, causing obstruction to blood flow and activation of inflammatory cytokines. Blocked capillaries cause localised areas of ischaemia with microaneurysms, and inflammation provokes oedema and hard exudates on the retina. (27) Ischaemia induces proliferation of new capillaries (neovascularisation) that are fragile and prone to haemorrhage. Neovascularisation and accompanying fibrosis cause loss of vision and may induce retinal detachment. (10,27)

Diabetic encephalopathy

This is becoming increasingly recognised as a long-term complication of both T1DM and T2DM. Vascular dementia, Alzheimer's disease and cognitive impairments are more common in people with diabetes. Underlying mechanisms are uncertain but microvascular damage, oxidative stress and toxicity combined with the effects of macrovascular disease and atherosclerosis probably all contribute. (29)

Early detection and treatment of complications of T2DM are essential for quality of life and cost reasons. (10) Variations in rate of complications between different groups of New Zealanders are not due solely to genetic differences. Initiatives that promote tight glycaemic control, management of other risk factors and early intervention when therapy fails, are essential if these differences are to be addressed.


Goals of therapy in T2DM are to lower PGC by addressing insulin resistance and abnormal pancreatic cell function. Preservation of beta cell function, weight reduction and reduction of cardiovascular risk are also essential. (30) Tight glycaemic control, with HbA1c less than seven percent, is regarded as optimal for decreasing risk of micro- and macrovascular complications. (31,26) However this should be determined for each individual, depending on risks of, and associated with, hypoglycaemia.

Initial treatment of T2DM involves intensive Lifestyle modification. In particular, increased exercise and weight reduction are demonstrated to reduce PGC by improving insulin resistance and possibly beta cell function. Decreased adipose tissue reduces dyslipidaemia, free fatty acid concentrations and secretion of inflammatory cytokines. (19) Increased exercise encourages the development of more skeletal muscle for glucose uptake and storage, and induces more mitochondria within existing muscle cells.

There is increased processing of fatty acids, preventing their accumulation inside the cells and reducing lipotoxicity. Insulin sensitivity of both skeletal muscle and liver cells is increased. (31,16)

Failure to maintain glycaemic control with Lifestyle modifications will determine the need for medication. Conventional drug therapy in T2DM addresses insulin resistance and/or insulin deficiency. More recent developments also address beta cell function and glucagon control. The major classes of drugs used in the treatment of T2DM are described below.

Drug therapy

Biguanides (Metformin): Metformin lowers PGC by increasing insulin-receptor sensitivity. Insulin resistance is decreased and glucose uptake increases. Glucose utilisation in liver and skeletal muscle is stimulated with increased glycogen synthesis and reduced gluconeogenesis. Dyslipidaemia is also improved, due to actions on adipose tissue. (11,33) Separate from its PGC Lowering actions, metformin may also exert an antioxidant effect and provide some protection against micro- and macrovascular complications. (33) It has been shown to reduce overall mortality compared to other oral hypoglycaemic agents. (34)

Metformin has no effect on insulin secretion, so carries Little risk of hypoglycaemia. It does not cause weight gain, unlike some other oral hypoglycaemic agents, and is useful for treatment in obese individuals.

Nausea, vomiting and other gastrointestinal (GI) effects occur in about 20 percent of people taking metformin. Slow upward titration of the dose can avoid these effects. (10)

Metformin is associated with a slight risk of lactic acidosis. This makes it unsuitable for use in people with cardiac, renal, liver or respiratory disease. However a recent Cochrane Review found no evidence of increased lactic acidosis with metformin. (34)

Sulphonylureas: These drugs act on beta celts to stimulate secretion of insulin from beta cells. Examples are glipizide, gliblencamide and gliclazide. There is an increased risk of hypoglycaemia with these drugs, especially gliblencamide, as they stimulate insulin secretion independent of PGC. About 20 percent of people on these drugs will have a hypoglycaemic episode each year. (35) Prescription of this class of drug should always be accompanied by education around prevention and detection of hypoglycaemia. (10)

Repaglinide is a meglitinide, similar to the sutphonylureas but with more rapid onset and shorter duration of action.

Glitazones (Thiazolidinediones): Pioglitazone and rosiglitazone are the two main drugs in this crass. Glitazones activate genes in adipose, skeletal muscle and liver celts that trigger increased fatty acid uptake and utilisation, and increase insulin sensitivity. They take up to two months to be effective. (11) Glitazones also stimulate sodium reabsorption in the kidneys, that causes fluid retention and oedema. These drugs cannot be used in people with heart failure, and there is an increased risk of bone fractures due to impaired osteobtast maturation.

Rosiglitazone (Avandia) has increased cardiovascular risks over pioglitazone. (36) It has been withdrawn from New Zealand, as of April 2011, following European withdrawal and increased restrictions on prescribing in the United States. (37)

Alpha-glucosidase inhibitors: Acarbose inhibits the digestion of carbohydrates in the gastrointestinal tract, thus slowing glucose absorption and preventing sharp increases in PGC after meats. (11) It is, however, associated with adverse GI effects.

Incretin therapies: GLP-1 mimetic drugs (such as exenitide) bind to GLP-1 receptors and exert similar effects in the body (see discussion above). GLP-1 is broken down in the body by the enzyme DPP4. Drugs that inhibit this enzyme (eg sitagliptin) prolong the action of natural incretins in the body. (13)

Amylin analogues: Pramlintide (Symlin) was developed in New Zealand. It is a synthetic amylin that does not form beta-cell-destroying plaques. Pramlintide is approved in the United States as a conjunctive therapy with insulin for type I diabetes. (13)


Current treatment guidelines work on the basis of therapeutic failure: treatment is continued until glycaemic control deteriorates and then further therapies are added.

Often there is a delay between failure, detection and initiation of new therapies, that results in prolonged periods of raised PGC. Ultimately, the person with T2DM may end up on insulin, as beta cell destruction leads to loss of endogenous insulin supplies.

Emerging therapies are aimed not just at glycaemic control but also preservation of beta-cell function and reversal of insulin resistance. Treatment paradigms need to be directed at slowing or stopping T2DM and beta cell loss, and reducing accompanying risk factors: obesity, hypertension and dyslipidaemia. This would involve earlier and more aggressive use of drugs therapies. (38,23)


T2DM is a complex disease with no single cure. New and more complex drug therapies are emerging as understanding of the fundamentals of T2DM grows. Treatment is moving beyond glycaemic control to address causative factors. Incidence of T2DM is increasing much more rapidly than anticipated, placing an increasing burden on the health budget and highlighting disparities in health outcomes between different groups of New Zealanders. Nurses play key roles in education, screening and treatment programmes. Knowledge of the underlying pathophysiology and drug therapy, supports treatment decisions when providing care to people with T2DM. *

What is HbA1c?

It is a measure of glycated haemoglobin. Glucose binds to haemoglobin A molecules in a concentration-dependent manner. Once bound, it cannot be removed. HbA1c gives an indication of the amount of glucose haemoglobin has been exposed to during the lifetime of the red blood cells.

Measured every four to 12 weeks until stable, HbA1c allows a more global view of a person's glycaemic control.

Results are given as a percentage: the HbA1c goat for tight gtycaemic control is seven percent. Internationally, art testing laboratories are moving to a new form of reporting HbA1c, reporting results in millimoles of glucose per mote of haemoglobin (mmol/ mol). For seven percent, the new resutt will be 53mmol/mol.


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Georgina Casey, RN, BSc, PGDipSci, MPhil (nursing), is the director of She has an extensive background in nursing education and clinical experience in a wide variety of practice settings.
Table 1. Factors stimulating release of insulin from the pancreas

Nutrients                      Glucose
                               Amino acids
                               Fatty acids

Incretins: gastrointestinal    Glucose-dependent insulinotropic
(released by eating)           hormones peptide (GIP)
                               Glucagon-like peptide 1 (GLP-1)

Nervous system                 Parasympathetic stimulation

Drugs that act on              Sulphonylureas (eg glipzide)
sulphonylurea receptors

Table 2. Differences between diabetic ketoacidosis (DKA) and
hyperosmolar hyperglycaemic non-ketotic syndrome (HHNS). (14,27)

                  OKA                         HHNS

Onset             Hours to days               insidious (weeks)

At risk           T1DM                        T2DM
                  T2DM in acute metabolic
                  stress states

Triggers          Untreated hyerglycaemia     Untreated hyerglycaemia
                  Metabolic stress            Metabolic stress
                  Acute infection             Acute infection
                  Non-compliance with         Non-compliance with
                  insulin                     medication
                                              Very high carbohydrate

Pathophysiology   Absolute lack of insulin    Some insulin present so
                  triggers ketogenesis        no ketones formed.
                  which causes metabolic      Hyperglycaemia causes
                  acidosis.                   hypersomolar diuresis
                  Ketones plus                dehydration and acute
                  hyperglycaemia cause        circulatory collapse.
                  osmotic diuresis and

Mortality         1-10%                       10-40%

Presentation      Polyuria, polydipsia,       Polyuria, polydipsia.
                  weight Loss.                Progressive decline in
                  Vomiting, abdominal pain.   consciousness.
                  Lethargy.                   Hemiparesis,
                  Signs of dehydration eg     disorientation, seizures.
                  hypotension, decreased      Signs of dehydration eg
                  skin turgor.                hypotension, decreased
                                              skin turgor.
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Author:Casey, Georgina
Publication:Kai Tiaki: Nursing New Zealand
Geographic Code:8NEWZ
Date:Mar 1, 2011
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